rs1425756773

Variant names:

• chr16-53480-C-A
• rs1425756773
• NM_016310.5:c.107G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-53480-C-A
• chr16-53480-C-G
• chr16-53480-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016310.5(POLR3K):​c.107G>T​(p.Arg36Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,878 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: POLR3K NM_016310.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.64

Genes affected

POLR3K (HGNC:14121): (RNA polymerase III subunit K) This gene encodes a small essential subunit of RNA polymerase III, the polymerase responsible for synthesizing transfer and small ribosomal RNAs in eukaryotes. The carboxy-terminal domain of this subunit shares a high degree of sequence similarity to the carboxy-terminal domain of an RNA polymerase II elongation factor. This similarity in sequence is supported by functional studies showing that this subunit is required for proper pausing and termination during transcription. Pseudogenes of this gene are found on chromosomes 13 and 17.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR3K	NM_016310.5	c.107G>T	p.Arg36Leu	missense_variant	Exon 1 of 3	ENST00000293860.6	NP_057394.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR3K	ENST00000293860.6	c.107G>T	p.Arg36Leu	missense_variant	Exon 1 of 3	1	NM_016310.5	ENSP00000293860.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456878 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 724572

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	0.0096	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.98
Eigen	Benign	0.049
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.20
Sift	Benign	0.21	T
Sift4G	Benign	0.21	T
Vest4		0.65
MutPred		0.50		Loss of solvent accessibility (P = 0.0098);
MVP		0.36
MPC		0.52
ClinPred		0.97	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1425756773; hg19: chr16-103480;